This project, part of a long-term goal to determine the role played by membrane receptors for growth factors in the control of normal and neoplastic cell growth, will focus on the receptors for insulin and epidermal-growth-factor/urogastrone (EGF/URO). The receptor for insulin present in cultured human fibroblasts, SV-40 transformed mouse embryo fibroblasts (SVAL/N) and in both diploid (SHE) and chemically transformed tumorigenic (BP6T) syrian hamster embryo fibroblasts will be studied in detail, so as to clarity the relationship between the receptor(s) in these cells and the insulin receptor previously characterized in adipocytes and liver. The comparative receptor characteristics will be evaluated by: (1) ligand binding studies with 1251-insulin for intact cells, and for both pariculate and soluble membrane preparations; (2) affinity chromatography on lectin-and insulin-agarose derivatives; (3) receptor perturbation by chemical, lectin and enzymatic probes; (4) electrophoretic analysis subsequent to covalent affinity labeling of the receptors; and (5) the interaction of the receptors with other non-receptor membrane glycoproteins. Similar studies will be done for the EGF/URO receptor so as to provide comparative data for two independent receptors related to cell growth. The studies should confirm or disprove the heretofore presumed identity of the fibroblast insulin receptor(s) with the insulin receptor previously characterized, either to establish a potential role for insulin as a growth factor for both normal and tumorigenic cells or to suggest a role for an as yet undiscovered insulin-like polypeptide. Further, a comparison of the receptor for insulin and EGF/URO from tumorigenic BP6T;SVAL/N) and parent strain (SHE;AL/N) fibroblasts will be possible; The data will interpreted in the context of the biochemical actions of insulin and EGF/URO on the cultured cells (membrane transport; DNA, RNA and protein synthesis) as determined by previously developed methods. The results will provide a firm basis for the subsequently planned studies of receptor regulation.